Magnetic Resonance Imaging (MRI) is a crucial diagnostic modality in modern medical practice, offering non-invasive insight into internal structures and functions of the human body. The development of MRI contrast agents has significantly improved imaging sensitivity and precision. Traditional gadolinium-based agents, while effective, have been linked to nephrogenic systemic fibrosis (NSF), necessitating the exploration of alternative contrast agents. Nanoparticle-based systems have emerged as promising candidates for new contrast media, leveraging the unique properties of nanoparticles to address technological and medical challenges. Manganese has garnered attention due to its potential as a safe and effective alternative to gadolinium-based agents. This study delves into the synthesis of manganese loaded nanoparticles using poly (lactic-co-glycolic acid) (PLGA), a biodegradable polymer with proven biocompatibility. Two distinct manganese nanoencapsulation methods were devised and evaluated for their toxicity profiles. The method demonstrating superior biocompatibility, designated as PLGA-MN, was selected for in vivo assessments. Comparative analysis was performed against a control group administered manganese acetate (MnAc) (PBS) solution. In vivo MR imaging was performed on Sprague-Dawley rats, while the distribution of PLGA-MNs in blood, brain, liver, and spleen was determined through inductively coupled plasma mass spectrometry (ICP-MS). The results lay the foundation for advancing contrast agent development, harnessing nanotechnology to elevate diagnostic imaging capabilities and simultaneously addressing the safety considerations linked to conventional agents such as gadolinium.